Application of carbon monoxide in kidney and heart transplantation: A novel pharmacological strategy for a broader use of suboptimal renal and cardiac grafts
Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmacological Research
Abstract
Carbon monoxide (CO) was historically regarded solely as a poisonous gas that binds to hemoglobin and reduces
oxygen-carrying capacity of blood at high concentrations. However, recent findings show that it is endogenously
produced in mammalian cells as a by-product of heme degradation by heme oxygenase, and has received a
significant attention as a medical gas that influences a myriad of physiological and pathological processes. At low
physiological concentrations, CO exhibits several therapeutic properties including antioxidant, antiinflammatory,
anti-apoptotic, anti-fibrotic, anti-thrombotic, anti-proliferative and vasodilatory properties,
making it a candidate molecule that could protect organs in various pathological conditions including cold
ischemia-reperfusion injury (IRI) in kidney and heart transplantation. Cold IRI is a well-recognized and
complicated cascade of interconnected pathological pathways that poses a significant barrier to successful outcomes
after kidney and heart transplantation. A substantial body of preclinical evidence demonstrates that CO
gas and CO-releasing molecules (CO-RMs) prevent cold IRI in renal and cardiac grafts through several molecular
and cellular mechanisms. In this review, we discuss recent advances in research involving the use of CO as a
novel pharmacological strategy to attenuate cold IRI in preclinical models of kidney and heart transplantation
through its administration to the organ donor prior to organ procurement or delivery into organ preservation
solution during cold storage and to the organ recipient during reperfusion and after transplantation. We also
discuss the underlying molecular mechanisms of cyto- and organ protection by CO during transplantation, and
suggest its clinical use in the near future to improve long-term transplantation outcomes.
Description
Research Article
Keywords
Carbon monoxide (CO), Carbon monoxide-releasing molecules (CORMs), Kidney and heart transplantation, Cold ischemia-reperfusion injury (IRI), Static cold storage (SCS)